Myeloid and lymphoid lineage C9orf72 regulates the IL-17 inflammatory axis in mice

The goal of this study was to identify cell types and pathways that contribute to autoimmunity and inflammation in C9orf72 loss of function mice. Overall design: The experimental design involved age matched euthanasia of C9orf72 mutant and control mice paired with mass cytometry, flow cytometry, single cell sequencing, antibody-based therapeutic neutralization and cellular and biofluidic analyses. Pre-defined euthanasia criteria, age for euthanasia and sample sizes were determined based on power calculations and temporal characterization of systemic and neural inflammation in this model. Neutrophil counts, platelet counts, and rotarod performance was used to assign mice into isotype antibody or anti-IL17A antibody treatment groups so these disease measures did not differ between C9or72-/- mice prior to treatment. All subjects were coded so operators remained blinded to genotype during behavioral testing, tissue harvest and outcome assessments. Numbers of mice and well replicates are indicated in figure legends.